Clarithromycin adverse reactions
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
Adverse Reactions
The most frequent and common adverse reactions related to clarithromycin therapy for both adult and pediatric populations are abdominal pain, diarrhea, nausea, vomiting and dysgeusia. These adverse reactions are consistent with the known safety profile of macrolide antibiotics.
There was no significant difference in the incidence of these gastrointestinal adverse reactions during clinical trials between the patient population with or without preexisting mycobacterial infections.
Adverse Reactions Observed During Clinical Trials of Clarithromycin
The following adverse reactions were observed in clinical trials with clarithromycin at a rate greater than or equal to 1%:
Gastrointestinal Disorders
Diarrhea, vomiting, dyspepsia, nausea, abdominal pain
Hepatobiliary Disorders
Liver function test abnormal
Immune System Disorders
Anaphylactoid reaction
Infection and Infestations
Nervous System Disorders
Dysgeusia, headache
Psychiatric Disorders
Insomnia
Skin and Subcutaneous Tissue Disorders
Rash
Other Adverse Reactions Observed During Clinical Trials of Clarithromycin
The following adverse reactions were observed in clinical trials with clarithromycin at a rate less than 1%:
Blood and Lymphatic System Disorders
Leukopenia, neutropenia, thrombocythemia, eosinophilia
Cardiac Disorders
Electrocardiogram QT prolonged, cardiac arrest, atrial fibrillation,extrasystoles, palpitations
Ear and Labyrinth Disorders
Vertigo, tinnitus, hearing impaired
Gastrointestinal Disorders
Stomatitis,glossitis, esophagitis, gastrooesophageal reflux disease, gastritis, proctalgia, abdominal distension, constipation, dry mouth, eructation, flatulence
General Disorders and Administration Site Conditions
Malaise, pyrexia, asthenia, chest pain, chills, fatigue
Hepatobiliary Disorders
Cholestasis, hepatitis
Immune System Disorders
Infections and Infestations
Cellulitis, gastroenteritis, infection, vaginal infection
Investigations
Blood bilirubin increased, blood alkaline phosphatase increased, blood lactate dehydrogenase increased, albumin globulin ratio abnormal
Metabolism and Nutrition Disorders
Anorexia, decreased appetite
Musculoskeletal and Connective Tissue Disorders
Myalgia, muscle spasms, nuchal rigidity
Nervous System Disorders
Dizziness, tremor, loss of consciousness, dyskinesia, somnolence
Psychiatric Disorders
Anxiety, nervousness
Renal and Urinary Disorders
Blood creatinine increased, blood urea increased
Respiratory, Thoracic and Mediastinal Disorders
Asthma, epistaxis, pulmonary embolism
Skin and Subcutaneous Tissue Disorders
Urticaria, dermatitis bullous, pruritus, hyperhidrosis, rash maculo-papular
In the acute exacerbation of chronic bronchitis and acute maxillary sinusitis studies overall gastrointestinal adverse events were reported by a similar proportion of patients taking either BIAXIN tablets or BIAXIN XL tablets; however, patients taking BIAXIN XL tablets reported significantly less severe gastrointestinal symptoms compared to patients taking BIAXIN tablets. In addition, patients taking BIAXIN XL tablets had significantly fewer premature discontinuations for drug-related gastrointestinal or abnormal taste adverse events compared to BIAXIN tablets.
In community-acquired pneumonia studies conducted in adults comparing clarithromycin to erythromycin base or erythromycin stearate, there were fewer adverse events involving the digestive system in clarithromycin-treated patients compared to erythromycin-treated patients (13% vs 32%; p < 0.01). Twenty percent of erythromycin-treated patients discontinued therapy due to adverse events compared to 4% of clarithromycin-treated patients.
In two U.S. studies of acute otitis media comparing clarithromycin to amoxicillin/potassium clavulanate in pediatric patients, there were fewer adverse events involving the digestive system in clarithromycin-treated patients compared to amoxicillin/potassium clavulanate-treated patients (21% vs. 40%, p < 0.001). One-third as many clarithromycin-treated patients reported diarrhea as did amoxicillin/potassium clavulanate-treated patients.
Post-Marketing Experience
The following adverse reactions have been identified during post approval use of clarithromycin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders
Thrombocytopenia, agranulocytosis
Cardiac Disorders
Torsades de pointes, ventricular tachycardia, ventricular arrhythmia
Ear and Labyrinth Disorders
Deafness was reported chiefly in elderly women and was usually reversible.
Gastrointestinal Disorders
Pancreatitis acute, tongue discoloration, tooth discoloration was reported and was usually reversible with professional cleaning upon discontinuation of the drug. There have been reports of BIAXIN XL tablets in the stool, many of which have occurred in patients with anatomic (including ileostomy or colostomy) or functional gastrointestinal disorders with shortened GI transit times. In several reports, tablet residues have occurred in the context of diarrhea. It is recommended that patients who experience tablet residue in the stool and no improvement in their condition should be switched to a different clarithromycin formulation (e.g. suspension) or another antibacterial drug.
Hepatobiliary Disorders
Hepatic failure, jaundice hepatocellular. Adverse reactions related to hepatic dysfunction have been reported with clarithromycin (see WARNINGS - Hepatotoxicity).
Immune System Disorders
Anaphylactic reaction
Infections and Infestations
Investigations
Prothrombin time prolonged, white blood cell count decreased, international normalized ratio increased. Abnormal urine color has been reported, associated with hepatic failure.
Metabolism and Nutrition Disorders
Hypoglycemia has been reported in patients taking oral hypoglycemic agents or insulin.
Musculoskeletal and Connective Tissue Disorders
Myopathy, rhabdomyolysis was reported and in some of the reports, clarithromycin was administered concomitantly with statins, fibrates, colchicine or allopurinol (see Contraindications And WarningS).
Nervous System Disorders
Convulsion, ageusia, parosmia, anosmia, paraesthesia
Psychiatric Disorders
Psychotic disorder, confusional state, depersonalization, depression, disorientation, manic behavior, hallucination, abnormal behavior, abnormal dreams. These disorders usually resolve upon discontinuation of the drug.
There are no data on the effect of clarithromycin on the ability to drive or use machines. The potential for dizziness, vertigo, confusion and disorientation, which may occur with the medication, should be taken into account before patients drive or use machines.
Renal and Urinary Disorders
Nephritis interstitial, renal failure
Skin and Subcutaneous Tissue Disorders
Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS), Henoch-Schonlein purpura, acne
Vascular Disorders
Hemorrhage
There have been reports of colchicine toxicity with concomitant use of clarithromycin and colchicine, especially in the elderly, some of which occurred in patients with renal insufficiency. Deaths have been reported in some such patients (see warnings and precautions).[1]
References
Adapted from the FDA Package Insert.